Carbonic anhydrase (CA) form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and proton or vice versa to maintain pH homeostasis in the body. The active site of most carbonic anhydrases contains a zinc ion; they are therefore classified as metalloenzymes.
The family of carbonic anhydrases has several members. There are at least five distinct CA families (α, β, γ, δ and ε). The α-CAs are found in mammals. The α-CAs are divided into four broad subgroups, which, in turn, consist of several isoforms: cytosolic CAs (CA-I, CA-II, CA-III, CA-VII, and CA-XIII), mitochondrial CAs (CA-VA and CA-VB), secreted CAs (CA-VI), and membrane-associated CAs (CA-IV, CA-IX, CA-XII, CA-XIV, and CA-XV).
CA isozymes II, IX and XII have been associated with neoplastic processes, and they are potential histological and prognostic biomarkers of certain tumors [Nordfors et al. (2010), BMC cancer; 10:148]. CA-II is the most widely expressed member of the α-CA gene family, being present in virtually every human tissue and organ. The transmembrane enzyme, CA-IX, was first recognized as a novel tumor-associated antigen expressed in several types of human carcinomas as well as in normal gastrointestinal tissue. CA-IX has been functionally linked to cell adhesion, differentiation, proliferation and oncogenic processes, and its enzymatic activity is comparable to CA II. Another transmembrane CA isozyme, CA-XII, was first found in normal kidney tissue and renal cell carcinoma. Further studies have shown that it is expressed in several other tumors (Ulmasov et al. (2000)), but also in some normal organs such as the colon and uterus. High expression of CA-II, CA-IX and CA-XII in tumors, particularly under hypoxic conditions, has further suggested that these enzymes may functionally participate in the invasion process, which is facilitated by acidification of the extracellular space.